Globoid cell leukodystrophy (GLD) is a progressive disorder of the nervous system which is the consequence of a deficiency of galactosylceramide b-galactosidase. The disease occurs in both dogs and humans although there are subtle enzymatic differences between the species in terms of various beta-galactosidase activities. This investigation will characterize different beta-galactosidases in brain, serum, leukocytes, and cultured fibroblasts from dogs and humans. Various enzyme fraction procedures, especially isoelectric focusing will be utilized. Procedures for cell hybridization of cultured canine and human fibroblasts and selection of hybrid cells will be developed. Various genetic crosses will be made utilizing fibroblasts from humans and dogs with GLD. Fractionation of beta-galactosidase activities in the human-dog hybrid cells will be studied by isoelectric focusing. Cytogenetic analysis of the hybrid cells will be performed and attempts will be made to localize the genetic control of various beta-galactosidase activities to specific chromosomes in both species. The effects of psychosine on cellular structure and beta-galactosidase activities will be evaluated in both canine and human fibroblasts.